Determination of glucose concentration in tissue

Abstract

A method for determining and monitoring tissue glucose concentration, wherein a perfusion solution is conveyed as a liquid column through a microdialysis probe implanted in the tissue and is moved to a test cell preferably arranged outside the patient's body, the volumetric flow of the perfusion solution being reduced in its time average for the duration of the dialysis intervals (T 1 ) and the volume of the perfusion solution perfused through the microdialysis probe during each dialysis interval (T 1 ) being moved on in a consecutive transport interval (T 2 ) at a higher volumetric flow to the test cell and wherein the glucose content of the perfusion solution passing through the test cell is determined from continuously detected test signals, characterized in that before passing through the microdialysis probe the perfusion solution is mixed with glucose in order to set a predetermined initial concentration.

What is claimed is: 
     
       1. Method for determining and monitoring tissue glucose concentration, wherein a perfusion solution (18) is conveyed as a liquid column through a microdialysis probe (12) implanted in the tissue (10) and is moved to a test cell (14) preferably arranged outside the patient's body, the volumetric flow of the perfusion solution (18) being reduced in its time average for the duration of the dialysis intervals (T 1 ) and the volume of the perfusion solution (18) perfused through the microdialysis probe (12) during each dialysis interval (T 1 ) being moved on in a consecutive transport interval (T 2 ) at a higher volumetric flow to the test cell (14) and wherein the glucose content of the perfusion solution (18) passing through the test cell (14) is determined from continuously detected test signals, wherein before passing through the microdialysis probe (12) the perfusion solution (18) is mixed with glucose in order to set a predetermined initial concentration.   
     
     
       2. Method as claimed in claim 1, wherein the initial glucose concentration is set to be within the physiological range. 
     
     
       3. Method as claimed in claim 1, wherein the volumetric flow (dV 1  /dt) of the perfusion solution (18) is adjusted in such manner during the transport intervals (T 2 ) that the glucose content of the perfusion solution (18) changes less than 10%, preferably less than 5% when the solution passes through the microdialysis probe (12). 
     
     
       4. Method as claimed in claim 1, wherein the volumetric flow (dV 0  /dt) of the perfusion solution is adjusted in such manner during the dialysis intervals (T 1 ) that the glucose content of the perfusion solution (18) as it passes through the microdialysis probe (12) substantially equals the tissue glucose concentration. 
     
     
       5. Method as claimed in claim 1, wherein a base line value is determined from test signals picked up at the test cell (14) during the flow-through of the volume of the perfusion solution (18) perfused at the higher volumetric flow (dV 1  /dt). 
     
     
       6. Method as claimed in claim 1, wherein the concentration of the tissue glucose is determined from the extremum or from the integral value of the test signals detected at the test cell (14) during each transport interval (T 2 ). 
     
     
       7. Method as claimed in claim 5, wherein the ratio of extremum to base line value of the peak- or dip-shaped signal sequence of the test signals is formed and is multiplied by the value of the initial glucose concentration and if necessary by a predetermined calibration factor to determine the tissue glucose concentration. 
     
     
       8. Method as claimed in claim 6, wherein the time separation of the extrema of the measurement values predetermined by the time interval (T 1  +T 2 ) of the transport intervals T 2  is monitored to check the validity of the test signals. 
     
     
       9. Method as claimed in claim 2, wherein the signal sequence of the test signals detected during each transport interval (T 2 ) at the test cell (14) is analyzed to check the validity of the determined glucose content, a peak being expected as a valid signal shape when the concentration value is higher than the adjusted initial glucose concentration and a dip being expected for a lesser concentration. 
     
     
       10. Method as claimed in claim 2, wherein the initial glucose concentration is set at a sugar-deficiency value and that upon a dip in the sequence of the test signals a sugar-deficiency alarm is emitted. 
     
     
       11. Method as claimed in claim 2, wherein the initial glucose concentration is set in alternating phases to a sugar-deficiency value and to a sugar-excess value and that, upon a dip in the sequence of the test signals during the phase set to sugar-deficiency concentration, and upon a peak of the phase set to excess-sugar concentration, an alarm signal is emitted. 
     
     
       12. Method as claimed in claim 1, wherein the extrema determined in the time interval (T 1  +T 2 ) of the transport intervals (T 2 ) are compared with the particular associated base line value to achieve qualitative pattern recognition of the sequence of the test signals, a peak being recognized as a signal shape when the extremum compared the the base line value is larger and a dip when the extremum is smaller. 
     
     
       13. Method as claimed in claim 1, wherein during each dialysis interval (T 1 ) the perfusion solution (18) is moved in several batches (36) mutually apart by a time interval (38) through the microdialysis probe (12). 
     
     
       14. Method as claimed in claim 13, wherein at each batch (36) a volume of the perfusion solution (18) essentially corresponding to the content of the microdialysis probe (12) is moved on.